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Status |
Public on Jul 01, 2013 |
Title |
A functional liaison between E2F and the aberrant ETS oncogene EWS/FLI1 in Ewing's sarcoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Translocations of ETS transcription factors are driver mutations in diverse cancers. We investigated the genomic network of the ETS fusion EWS/FLI1 in Ewing's sarcoma (ESFT) as a model of ETS-driven tumorigenesis. ChIP-Seq and transcriptional analysis identified E2F3 as a principle co-factor of EWSFLI1 defining functionally distinct gene sets. While EWS/FLI1 binding independent of E2F3 predominantly associated with repressed differentiation genes, significant co-localization with E2F3 was discovered at proximal promoters of activated growth-related genes. Thus, EWS/FLI1 promotes oncogenesis by simultaneously perturbing differentiation state and augmenting the expression of genes co-regulated by E2F3. Integration of additional E2F3 and ERG localization data from prostate cancer containing TMPRSS2/ERG verified that the ETS-E2F module is also found in prostate cancer and may be of general relevance to ETS driven cancers.
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Overall design |
Timecourse with 6 timepoints of a doxicyclin inducible EWS-FLI1 knockdown in the A673 Ewing's Sarcoma celline
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Contributor(s) |
Bilke S, Schwentner R, Yang F, Kauer M, Walker RL, Kovar H, Meltzer PS |
Citation(s) |
23940108 |
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Submission date |
Feb 25, 2011 |
Last update date |
Dec 06, 2018 |
Contact name |
Maximilian Kauer |
E-mail(s) |
maximilian.kauer@ccri.at
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Organization name |
CCRI, St.Anna Children Cancer Research Institute
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Department |
Molecular Biology
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Lab |
Heinrich Kovar
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Street address |
Zimmermannplatz 10
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City |
Vienna |
ZIP/Postal code |
1090 |
Country |
Austria |
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Platforms (1) |
GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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Samples (16)
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Relations |
BioProject |
PRJNA137111 |